Lysophosphatidyl Choline Induced Demyelination in Rat Probed by Relaxation along a Fictitious Field in High Rank Rotating Frame

Lauri J. Lehto, Aloma A. Albors, Alejandra Sierra, Laura Tolppanen, Lynn E. Eberly, Silvia Mangia, Antti Nurmi, Shalom Michaeli, Olli Gröhn

In this work a new MRI modality entitled Relaxation Along a Fictitious Field in the rotating frame of rank 4 (RAFF4) was evaluated in its ability to detect lower myelin content in lysophosphatidyl choline (LPC)-induced demyelinating lesions. The lesions were induced in two areas of the rat brain with either uniform or complex fiber orientations, i.e., in the corpus callosum (cc) and dorsal tegmental tract (dtg), respectively. RAFF4 showed excellent ability to detect demyelinated lesions and good correlation with myelin content in both brain areas. In comparison, diffusion tensor imaging metrices, fractional anisotropy, mean diffusivity and axonal and radial diffusivity, and magnetization transfer (MT) metrices, longitudinal relaxation during off-resonance irradiation and MT ratio, either failed to detect demyelination in dtg or showed lower correlation with myelin density quantified from gold chloride stained histological sections. Good specifity of RAFF4 to myelin was confirmed by its low correlation with cell density assesed from Nissl stained sections as well as its lack of sensitivity to pH changes in the physiological range as tested in heat denaturated bovine serum albumin phantoms. The excellent ability of RAFF4 to detect myelin content and its insensitivity to fiber orientation distribution, gliosis and pH, together with low specific absorption rate, demonstrates the promise of rotating frame of rank n (RAFFn) as a valuable MRI technique for non-invasive imaging of demyelinating lesions.